Although murine typhus occurs in diverse habitats in many parts of the world and has been an important cause of human disease in certain areas, there still are many unexplained features about the vector biology and transmission of this zoonosis, especially since a variety of ectoparasites and small mammals are deeply involved. In this study we will continue to use modern quantitative methods to examine, under controlled conditions in the laboratory, selected components and inter-relationships of the pathogen-vector-host complex. As has been shown by the results to date, such information can contribute to our understanding of the encology of murine typhus; for example, we have provided evidence indicating that cat flea (Ctenocephalides felis) and the rat flea Leptopsylla segnis should be regarded as potential vectors. For the first time, transovarial transmission of the infection to the next generation of fleas has been demonstrated. This finding raises the possibility that fleas may serve to perpetuate the cycle of murine typhus infection in nature. Data are provided suggesting that murine typhus may perhaps be transmitted by the bite of the flea, and not merely by contact with feces or tissues of infected fleas. Such observations may change our concepts about the transmission of this rickettsiosis and hence affect recommendaions for its control. Our objectives include: 1) to investigate in detail the quantitative interactions between Rickettsia mooseri including means of transmission and the course of infection in four species of fleas (Xenopsylla cheopis, Ctenocephalides felis, Leptopsylla segnis and Echidnophaga gallinacea) and the rat losue (Polyplax spinulosa); 2) to study host immunological responses to flea infection which may affect the acquisition and transmission of R. mooseri; and 3) to study the reservoir mechanisms including vertical transmission in fleas and reactivation of latent infection in rats, using natural stress such as pregnancy and parasite or immunosuppressive drugs such as cyclophosphamide.